Among the many risk factors for premature coronary artery disease, plasma cholesterol and, perhaps, triglyceride levels, have been shown to be important. The objective of this proposal is to determine the specific pathologic abnormality in each genetic form of hypertriglyceridemia, some of which are associated with a marked increase in risk for premature coronary artery disease, while others are not. Using cultured skin fibroblasts obtained from individuals with these disorders, and studying these individuals on the Clinical Research Center, studies will be performed to examine factors that control the synthesis and catabolism of the various components of the plasma lipoproteins, their precursors and products. With elucidation of the specific genetic defect in each disorder, one will be able to identify those individuals at high risk for coronary artery disease and to direct therapy at the specific defect.